Beta amiliode

Original Research Article
Dement Geriatr Cogn Disord 2008;26:522–527 DOI: 10.1159/000178756
Accepted: October 1, 2008 Published online: December 2, 2008

Serum Amyloid P Component as a Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease
Nicolaas A. Verwey a, b Alie Schuitemaker a, c Wiesje M. van der Flier a Sandra D. Mulder b Cees Mulder b C. Erik Hack b Philip Scheltens aMarinus A. Blankenstein b Robert Veerhuis b, d
Departments of a Neurology, b Clinical Chemistry, c Nuclear Medicine and PET Research, and d Pathology and Psychiatry, Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands

Key Words Alzheimer’s disease Mild cognitive impairment Serum amyloid P component Cerebrospinal fluid Biomarker

val = 0.9–5.4). Conclusion: Our data suggestthat measurement of CSF SAP levels can aid in the identification of incipient AD among MCI patients.
Copyright © 2008 S. Karger AG, Basel

Abstract Background: Serum amyloid P component (SAP), present in amyloid- (A ) plaques in Alzheimer’s disease (AD), may protect A deposits against proteolysis, thereby promoting plaque formation. The aim was to investigate if SAP levels in cerebrospinal fluid(CSF) and serum can be used to discriminate controls, AD and mild cognitive impairment (MCI) patients, and to identify incipient AD among MCI patients. Methods: SAP levels in CSF and serum were determined in 30 controls, 67 MCI and 144 AD patients. At follow-up, 39 MCI patients had progressed to dementia, while 25 had remained stable (mean follow-up time: 2.6 8 1.0 and 2.1 8 0.8 years). Results:Cross-sectionally no differences were found in SAP levels in CSF and serum between the groups. MCI patients that had progressed to dementia at follow-up had lower CSF SAP levels (13 mg/l, range 3.3–199.3 mg/l) than MCI nonprogressors (20.2 mg/l, range 7.0–127.7 mg/l; p ! 0.05). A low CSF SAP level was associated with a 2-fold increased risk of progression to AD (hazard ratio = 2.2; 95% confidenceinter-

Introduction

Mild cognitive impairment (MCI) is characterized by an isolated memory deficit and a largely intact general cognitive functioning [1]. Patients with MCI are at a high risk of developing dementia of which Alzheimer’s disease (AD) is the most common form [2, 3]. Early identification of MCI patients that progress to dementia is important in view of future therapeuticoptions. However, diagnosing incipient or prodromal AD in MCI patients remains a difficult issue and thus there is a need for biomarkers that discriminate stable MCI cases from MCI patients who will progress to AD. Neuropathologically AD is characterized by neurofibrillary tangles and amyloid- (A ) plaques [4]. A number of inflammation-related factors, including serum amyloid P component (SAP),accumulate in A plaques [5–9]. Human SAP is a glycoprotein that exists as a penN.A. Verwey, MD Department of Clinical Chemistry, VU University Medical Center PO BOX 7057 NL–1007 MB Amsterdam (The Netherlands) Tel. +31 20 4443 868, Fax +31 20 4443 895, E-Mail n.verwey@vumc.nl

© 2008 S. Karger AG, Basel 1420–8008/08/0266–0522$24.50/0 Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Accessibleonline at: www.karger.com/dem

tameric ring-like structure of noncovalently bound subunits in serum [10]. SAP binds a variety of ligands, including A , in a Ca2+-dependent manner [11, 12]. SAP binding to its ligands can, in turn, lead to binding of complement factor C1q and initiate activation of the classical pathway of the complement system. SAP binding to newly formed amyloid fibrils mayprotect the A deposits from proteolysis, and as a consequence promote A fibril and amyloid plaque formation in the brain [11, 13–16]. Clustering of activated microglial cells in A plaques was observed in SAP- and C1q-containing A plaques preceding tau-related neurodegenerative changes [17]. In vitro, SAP and C1q inhibit the microglial uptake of A [18]. This inability to remove A in the presence of...